acid and anion

Oxygenation

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The First Concernthe first concern in any life threatening illness is to maintain an adequate supply of oxygen to sustain oxidative metabolism[Marino 2nd ed.]

The Oxygenation Profile ABG Overview Allows evaluation of arterial oxygen Sa02 Pa02

Allows evaluation of alveolar (pulmonary) oxygen A-a gradient P/F ratio

Allows evaluation of serum-cellular environment pH

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PaO2-FiO2 ratio

Normal PaO2/FiO2 is 300-500 7.45 Alkalosis: a primary physiologic process that, occurring alone, tends to cause alkalemia. Examples: metabolic alkalosis from excessive diuretic therapy; respiratory alkalosis from acute hyperventilation. If the patient also has an acidosis at the same time, the resulting blood pH may be high, normal, or low.

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Acid-base Terminology

Primary acid-base disorder: One of the four acidbase disturbances that is manifested by an initial change in HCO3- or PaCO2. Compensation: The change in HCO3- or PaCO2 that results from the primary event. Compensatory changes are not classified by the terms used for the four primary acid-base disturbances.

The Oxygenation ProfileAcid-Base Disturbances Are common in critical patients May be complex or mixed Are often confusing Requires accurate analysis to facilitate appropriate treatment Focus on Metabolic Acidosis

5 Step Approach Acidemic or Alkalemic : Check pH Is the overriding disturbance respiratory or metabolic? If respiratory, is it acute or chronic? If metabolic acidosis is present, is there an wide AG.

If metabolic acidosis disturbance is present is the respiratory system compensating adequately? WINTERS FORMULA. Are other metabolic disturbances present in a patient with a anion gap metabolic acidosis? This is the famous delta delta approach which aims at calculating the bicarbonate level before the generation of the anion gap acidosis. Measured bicarbonate + (AG 12)

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The ProfileComponents of the ABG and Chemistry Panel that are indicators in acid-base balance/imbalance. pH | pCO2 | pO2 | O2 Sat| (H+)HC03| Base| Total CO2

Direct measure of acid Inversely reflects acid (estimates one of the major buffers)

The ProfileCells: Producer Produces acid during metabolism: acid transported as carbonic acid Tissue acids increase in insulin deficiency states Tissue acids increase in tissue hypoxia states

Kidney: Regulator Major volume and electrolyte regulator Acid regulator Base regulator Lung: Acid regulator Rate and depth of breaths depends on the carbonic acid and therefore the pH

Cells: Regulate pH Acidosis: acid (H+) uptake in exchange for potassium release provides buffer effect and promotes intracellular hypokalemia Alkalosis: acid (H+) release in exchange for potassium uptake provides buffer effect and promotes intracellular hyperkalemia

The Profile Direct Effects from Acid : Presence or Absence pH: directly reflects acid When acid goes up, pH goes down Acids are formed as end products of protein, carbohydrate, and fat metabolism. To maintain the bodys normal pH (7.35-7.45), the H2C03 must be controlled: H+ must be neutralized (buffer and cells) or excreted (requires renal function) C02 must be regulated via ventilation

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Respiratory = PCO2pCO2is directly measured (not calculated), and is a reliable indicator of respiratory acid-base disturbances. The correlation between pCO2 and respiratory pH is direct, consistent, and linear.

And theres an equivalent measurement for metabolic

and its NOT bicarbIn pure metabolic disorders, bicarb is a useful measurement, but if youll remember the equilibrium formula: H20 + CO2 H2CO3 H+ + HCO3youll notice that HCO3 can be affected by respiratory (CO2) or metabolic (H+) components, and therefore isnt a specific marker for either. In fact, the relationship between metabolic acidosis and bicarbonate is neither consistent nor linear.

The Oxygenation Profile Direct Effects from Acid Presence or Absence CO2 = Acid CO2 = pH CO2 = pH

HCO3 - = Base (opposite of H+:acid) HCO3 - (think H+ {acid}) = pH HCO3 - (think H+ {acid}) = pH

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The ProfileCO2 + H2O H2CO3 H+ + HCO31. When carbonic acid goes up, pH goes down. 2. Attempts to compensate are made via the shift of carbonic acid to the unaffected side. Requiring increased clearance via ventilation (RR x Tidal volume) when the problem is either metabolic (tissue production) or renal (acid clearance, buffer production). Requiring increased renal clearance (increased carbonic acid presented to the kidney, separation of H+ from HC03 ) excreting acid and retaining buffer.

The Oxygenation ProfileCO2 + H2O H2CO3 H+ + HCO31. H2C03 is carbonic acid: when it increases pH goes down when it decreases pH goes up 2. C02 is a pre-form of H2C03: The partnership of C02 +H20 yields carbonic acid 3. H+ is a pre-form of H2C03: The partnership of H+ and HC03 yields carbonic acid 4. H+ is a byproduct of tissue metabolism and is increased when: 1.) metabolic disorders at the tissue level donate more H+ (hypoxia, failure of lactate-pyruvate conversion, ketosis) 2.)there is failure to clear acid (renal failure) and produce HC03 from H2C03

Modified Henderson and Hasselbalch Equation H+ = 24 x PCO2/HCO3 Equation emphasizes that the [H] depends on a ratio and not absolute concentrations.

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The Oxygenation Profile

CO2 + H2OCOMPENSATION Increase RR Increase Tidal Volume

H2CO3pH

H+ + HCO3PROBLEM Ketosis Lactic acidosis

If the problem is metabolic ( ketosis or lactic acidosis both increasing H+ production), compensation occurs via increasing the minute ventilation (RR x TV) and blowing off C02: Rapid compensatory mechanism: should occur immediately


CO2 + H2OPROBLEM Pulmonary failure

H2CO3pH

H+ + HCO3-

COMPENSATION Renal excretion of H+ Retaining HC03 Slow compensation

If the problem is ventilation failure ( C02 retention) , slow compensation requiring renal regulation occurs: H2C03 is separated in the renal tubules into H+ and HC03 -

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CO2 + H2O

H2CO3pH

H+ + HCO3-

In severe sepsis, it is common to see metabolic failure first ( H+ up) with respiratory compensation (C02 down). Eventually respiratory failure can follow. When both systems fail, the original and then the compensatory system, the carbonic acid , H2C03, will increase with no where to dissociate (cannot be shifted to its compensatory side). pH will drop sharply.

The Oxygenation ProfileAcid-Base Perfect Values (Acceptable range) pH= 7.40 (7.35 - 7.45) H2CO3 affects the ph (H2CO3 , pH )

PCO2 = 40 (35 45) HCO3- = 24 (22 - 26) opposite of H+

The Oxygenation Profile Interpretation of the arterial blood gas Determine 1) The problem is named by the direction of the pH in respect to perfect : acidosis or alkalosis When not perfect, the pH goes (from perfect) in the acid or alkaline direction Is the pH up (alkaline) or down (acid)?

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The Oxygenation Profile Determine Is the pH inside or outside the range of normal? Inside range May just be normal variation : PCO2. HCO3 - are within range of normal May be a problem , but compensation has occurred. Find the culprit which is the cause of the pH changed Outside range NEVER normal, always a primary problem NOT compensated, that is why the pH is out of range FREQUENTLY reflects two primary problems

The Oxygenation Profile Determine Step 2) The problem is named by the causative culprit which affects the pH Is the pH up (alkaline) or down (acid)? If the pH is down that reflects acid If the problem is respiratory, PCO2 has to be up If the problem is metabolic ( either production or regulation) , the HCO3 - has to be down, Remember, HCO3 moves inversely to H+ and what you really want to know about is the absence or presence of acid

The Oxygenation Profile NEVER normal NAME the problem

Determine Step 3) if the pH is down and outside range

PCO2 direct measure of acid, if the cause is PCO2 it goes in the opposite direction of the pH

HCO3 calculation of buffer (H+ assumed) think H+ and if the cause, H+ it goes in the opposite direction of the pH

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Step 4) if the pH is down, but inside range may be a normal variation ( all three measures within range) It is abnormal: If one of the two measures (PCO2,HCO3 ,(H+ assumed) is abnormal ( out of range ): Determine if the culprit is what caused the pH shift:

If yes, THERE HAS to be compensation from the other system, otherwise pH CANNOT be normal range

measures

CO2 4035-45

pH 7.40

Bicarb (H+)

perfect range note note note

24 (H+)

7.35-7.45 22-26

21 65 65

7.52 7.22 7.355

15 ( H+ ) 23( H+ ) 36

The Oxygenation ProfileMeasures perfect range sample CO2 40 35-45 44 pH 7.40 7.357.45 7.36 HCO3 (H+ ) 24 (perfect) 22-26 ( H+ - H+ ) 24 ( H+ perfect)

CO2 44, pH 7.36, HCO3 24

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www.barbaramclean.com

Case #1:

A 4 year old with chronic renal failure presents to the pedes ER with history of increasing azotemia, weakness, and lethargy. Exam reveals the patient to be modestly hypertensive, and tachypneic. Labs reveal BUN=100, and Creatinine=8. How can we tell if an acid-base disorder is present?

Case #1:

pH=7.37, PaCO2=22, and HCO3=12

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Is compensation appropriate?

HCO3 is decreased by 12 mmoles/l PaCO2 should decrease by 1 to 1.5 times the fall in HCO3; expect PaCO2 to decrease by 12-18 mm Hg or be between 22-28 mm Hg 24 (12)= 12 Pac02 1 to 1.5 times (bicarb) 40- 12 to 18 mmhg= 28-22 Pac02

The Oxygenation Profile Step 1: Name the problem: pH shift towards acid or alkaline (from perfect)

Step 2: Name the problem: pH inside or outside range

Step 3: Name the cause Causative factor must be what affects the pH

Step 4: Is there compensation pH within range but not perfect

The Oxygenation ProfileExample 1:pH = 7.26 : pH is a symptom of the primary problem: In this case acidosis!

pH is on the acid side and outside the range of normal. This is an acute problem (acute means the pH is out of range). Find the cause, using C02 and HC03 (H+)

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The Oxygenation ProfileCO2 = 60 mmHgCO2 = pH

ExamplepH = 7.26 CO2= 60 mmHg= acid CO2 = pH 1. Acute: pH out of range 2. Acidosis: pH down 3. Respiratory: C02 is up and out of range ( more acid: failure to ventilate)Name the initial problem: acute respiratoryacidosis

The Oxygenation ProfileExample 1

HCO3 = Base (opposite of H+ acid) HCO3 (think H+ {acid}) = pH HCO3 (think H+ {acid}) = pH Example pH = 7.26 CO2 = 60 mmHg= acid HCO3 = 28 ( up and slightly out of range, therefore H+ is slightly down: headed towards compensation) 1. Acute: pH out of range (if pH out of range, there is NOT compensation, never normal) 2. Acidosis: pH down 3. Respiratory: C02 is up and out of range ( more acid: failure to ventilate)Name the initial problem: acute respiratoryacidosis ( acute means uncompensated)

The Oxygenation ProfileAssessing Compensation Example; Five hours later HCO3 = Base (opposite of H+ acid) HCO3(think H+ {acid}) = pH HCO3 (think H+ {acid}) = pH Example pH = 7. 351 CO2 = 60 mmHg= acid HCO3 = 35 ( up and out of range, therefore H+ is down) Do you still have a problem? YES! acidosis (pH down but inside range) caused by ventilation failure ( C02 up and outside range) BUT if there is a problem (C02) and pH is in range there has to be compensation, and that only occurs from the non problem side ! RENAL: shifted the increase in carbonic acid ( C02 + H20 H2C03 which is then presented to the functional kidney which separates the H2C03 into HC03 and H+

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The Oxygeanation ProfileMeasures CO2 perfect range 40 35-45 21 pH 7.40 7.35-7.45 7.36 HCO3 (H+ ) 24 (perfect) 22-26 ( H+ - H+ ) 12 ( H+ )

CO2 21, pH 7.36, HCO312 ( H+

)

which removes C02. If the patient was hyperventilating and that was the problem, the pH would be up and alkalotic. When evaluating further, the low HC03 indicates a significant increase in H+ (metabolic acid). HC03 (H+ ) , pH but in range: Only way that happens is compensation! Answer:. Compensated metabolic acidosis. Compensated!! Increased metabolic acid causing increased carbonic acid is compensated with an increase in ventilation( C02 and RR )

Answer: Respiratory rate is 26. Patient is blowing off C02 and

Buffering Systems

A buffer is a chemical that can bind excessive H+ or OH without a significant change in pH A buffering pair consists of a weak acid and its conjugate base The most important plasma buffering systems are the carbonic acidbicarbonate system and hemoglobin

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Carbonic AcidBicarbonate Pair in both the lung and the kidney Operates The greater the partial pressure of carbon dioxide, the more carbonic acid is formed At a pH of 7.4, the ratio of bicarbonate to carbonic acid is 20:1 Bicarbonate and carbonic acid can increase or decrease, but the ratio must be maintained

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Carbonic AcidBicarbonate If the Pair amount of bicarbonate decreases, the pH

decreases, causing a state of acidosis The pH can be returned to normal if the amount of carbonic acid also decreases This type of pH adjustment is referred to as compensation

The respiratory system compensates by increasing or decreasing ventilation The renal system compensates by producing acidic or alkaline urine

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Carbonic AcidBicarbonate Pair

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Other Buffering Systems Protein buffering Proteins have negative charges, so they can serve as buffers for H+ Renal buffering Secretion of H+ in the urine and reabsorption of HCO3 Cellular ion exchange Exchange of K+ for H+ in acidosis and alkalosis

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Buffering Systems

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Metabolic Alkalosis

Respiratory compensation raises PCO2 by 0.7 mmHg for every 1 meq/L rise in HCO3 Causes include vomiting, intake of alkali, diuretics, or very commonly, NG suction without the use of proton-pump inhibitors or H2 blockers

Respiratory Acidosis Compensation occurs in 2 steps 1. Cell buffering that acts within minutes to hours 2. Renal compensation that is not complete for 3-5 days

IN ACUTE: Bicarb rises 1 meq/L for every 10 mmHg elevation in PCO2 or for every 1 up of PCO2, pH should fall .0075

IN CHRONIC: Bicarb rises 3.5 for every 10 or for every 1 up of PCO2, pH should fall .0025 due to tighter control of pH by increased renal excretion of acid as ammonium

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Respiratory Alkalosis

ACUTE: Plasma bicarb falls by 2 for every 10 fall in PCO2 CHRONIC: Bicarb falls by 4 for every 10 fall in PCO2

Anion Gap

If Metabolic acidosis is present, is anion gap wide (> 20)?

Calculate the anion gap (AG). If the anion gap is 20, there is a primary metabolic acidosis regardless of pH or serum bicarbonate concentration. The acidosis is due to increased H+ Gap is generally wide only with metabolic ACID production ( Lactic Acid/ Ketoacid) Principle: The body does not generate a wide anion gap as a compensatory mechanism for a primary disorder. With a wide AG, metabolic acidosis is ALWAYS the primary disorder!

Anion GapAnion gap is a concept used to estimate electrolyte (anions & cation) levels in the serum and {measures or estimates the , sic} conditions that influence them (Tabers Cyclopedic Medical Dictionary, 2005). Normal Anion Gap = (Na+) - (Cl- + HCO3-) = 12 (+/- 2) Positive charged ions and negative charged ions are relatively equal in normal physiology. In vivo physiology all equal! The measured ions (lab analysis) are represented by Na+, Cl- and HC03- (or total serum C02), the external measured gap of 12 (+/- 2) is considered acceptable

Na+

(Cl - + HCO3-)

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Anion GapAnion Gap = (Na+) - (Cl- + HCO3-)

When there is an increase in unmeasured ions, there will be a gap between the + and measures A gap of > 20 implies a metabolic increase in acid production. Lactic Acid and Ketoacid donate H+ . H+ binds to HC03 and/or Cl changing the charge HC03 and/or Cl The gap between + and gets wide(Cl - + HCO3 -) : light on the negatives

(Lactic acid or ketones donated H+) Na+ constant

heavy on the positives

7.22 12

1. 145 - (12 + 122)= 11 2. 138- (12+ 104)= 22 149-( 12+90)= 47

Anion Gap Used to confirm type of metabolic acidosis with ABG Used to diagnose metabolic acidosis without ABG Affected by: albumin (for each 1 gm decrease in albumin , add three points to gap) hyperchloremia (usually from fluid resuscitation) High Cl- causes decrease in available HC03 High Cl- binds to H+ HCl Cannot compensate because is not a compound that can be blown off Metabolic acidosis with normal gap: non-gap acidosis most commonly occurs in hyperchloremia

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Anion GapMeasures CO2 perfect range 40 35-45 10 pH 7.40 7.357.45 7.31 HCO3 (H+ ) 24 (perfect) 22-26 ( H+ - H+ ) 5 (H+.

)

Answer: HC03 is down and outside of range which means H+ is upand outside of range: Acidosis. This is metabolic acidosis. Although there is an attempt to compensate, the ventilatory drive is at its limits. CO2 10, pH 7.31, HCO3 5, Na 135, Cl 90 Anion gap: Na (Cl HCO3) = 135 (90+5) = 135-95 = 40

Anion GapCO2 10, pH 7.31, HCO3 5, Na 135, Cl 90Anion gap: Na (Cl HCO3) = 135 (90+5) = 135-95 = 40

The wide anion gap supports the presence of increased metabolic acids! First question: What is the glucose and diabetic history? Second question: Does the patient have lactic acidosis? Third question: If neither, does history support acid ingestion?

Anion Gap chloride

Helps to identify the type of metabolic acidosis Non-anion gap acidosis Anion gap acidosis suggests DKA Lactic acidosis

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Watch Out In. Hypoalbuminemia

Decrease in unmeasured anions Increase in unmeasured cations Hypercalcemia Hypermagnesemia Hyperkalemia Multiple myeloma Lithium toxicity

ABG analysis

Respiratory compensation ( metabolic acidosis) results in 1.2 mm Hg fall in PCO2 for every 1 meq/L fall in bicarb pCO2 = 1.5 (HCO3) + 12 Winters formula Calculates expected PaCO2 for metabolic acidosis PaCO2 = 1.5 x HCO3 + 12

Determine anion gap (AG) AG = NA (HCO3+ CL) AG metabolic acidosis Non AG acidosis determined by delta gap

Calculating Gap Calculate the excess anion gap (total anion gap normal anion gap) and add this value to the measured bicarbonate concentration: if the sum is > than normal bicarbonate (> 30) there is an underlying metabolic alkalosis if the sum is less than normal bicarbonate (< 23) there is an underlying nonanion gap metabolic acidosis

1. Excess AG = Total AG Normal AG (12) 2. Excess AG + measured HCO3= > 30 or < 23? Principle: 1 mmol of unmeasured acid titrates 1 mmol of bicarbonate ( U anion gap = U [ HCO3])

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Why is this true?

For each 1 mmol acid titrated by the carbonic acid buffer system, 1 mmol of HCO3 is lost via conversion to CO2 and H2O and 1 mmol of the sodium salt of the unmeasured acid is formed. 1 mmol in HCO3 =1mmolin AG Therefore, the sum of the new (excess) anion gap and the remaining (measured) bicarbonate values should equal the normal bicarbonate concentration

ABG analysis Delta gap Delta HCO3 = HCO3 (electrolytes) + change in AG Delta gap < 24 = non AG acidosis Delta gap > 24 = metabolic alkalosis

The Oxygenation ProfileIs there more than one problem? Now evaluate the metabolic component of acid/base regulation remembering that the metabolic side is affected by Production of H+ (ketosis, lactic acidosis) Excess ingested acids (i.e., salicylate ) Excretion of acid (renal) Regulation of bicarbonate (renal, Chloride) Principle: There may be two sides to the problem. At the very least, you expect compensation to occur.

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Mixed Acid-base Disorders are Common In chronically ill respiratory patients, mixeddisorders are probably more common than single disorders In renal failure (and other conditions) Always be on the lookout for mixed acid-base disorders. They can be missed!

Tips to Diagnosing Mixed TIP 1. Do not interpret any blood gas data for Acid-base Disorders acid-base diagnosis

without closely examining the serum electrolytes: Na+, K+, Cl-, and CO2. A serum CO2 out of the normal range always represents some type of acidbase disorder (barring lab or transcription error). High-serum CO2 indicates metabolic alkalosis &/or bicarbonate retention as compensation for respiratory acidosis. Low-serum CO2 indicates metabolic acidosis &/or bicarbonate excretion as compensation for respiratory alkalosis. Note that serum CO2 may be normal in the presence of two or more acid-base disorders.

Tips to Diagnosing Mixed TIP 2. Single acid-base disorders do not lead to normal Acid-base Disorders (cont.)blood pH. Although pH can end up in the normal range (7.35 - 7.45) with a single mild acid-base disorder, a truly normal pH with distinctly abnormal HCO3- and PaCO2 invariably suggests two or more primary disorders. Example: pH 7.40, PaCO2 20 mm Hg, HCO3- 12 mEq/L in a patient with sepsis. Normal pH results from two co-existing and unstable acid-base disorders - acute respiratory alkalosis and metabolic acidosis.

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Tips to Diagnosing Mixed TIP 3. Simplified Disorders (cont) Acid-baserules predict the pH and HCO3- for agiven change in PaCO2. If the pH or HCO3- is higher or lower than expected for the change in PaCO2, the patient probably has a metabolic acid-base disorder as well.

Predicted changes in HCO3- for a directional change in PaCO2 can help uncover mixed acid-base disorders. A normal or slightly low HCO3- in the presence of hypercapnia suggests a concomitant metabolic acidosis, e.g., pH 7.27, PaCO2 50 mm Hg, HCO3- 22 mEq/L. Based on the rule for increase in HCO3- with hypercapnia, it should be at least 25 mEq/L in this example; that it is only 22 mEq/L suggests a concomitant metabolic acidosis. b) A normal or slightly elevated HCO3- in the presence of hypocapnia suggests a concomitant metabolic alkalosis, e.g., pH 7.56, PaCO2 30 mm Hg, HCO3- 26 mEq/L. Based on the rule for decrease in HCO3- with hypocapnia, it should be at least 23 mEq/L in this example; that it is 26 mEq/L suggests a concomitant metabolic alkalosis.

Tips to Diagnosing Mixed Acidbase In maximally-compensated metabolic acidosis, the TIP 4. Disorders (cont.)numerical value of PaCO2 should be the same (or close to) as the last two digits of arterial pH. This observation reflects the formula for expected respiratory compensation in metabolic acidosis: Expected PaCO2 = [1.5 x serum CO2] + (8 s 2)

In contrast, compensation for metabolic alkalosis (by increase in PaCO2) is highly variable, and in some cases there may be no or minimal compensation.

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Case #2:

A 15 year old female is brought to the pedes ER in an obtunded state. Per her family, patient history is notable for progressive weakness/malingering over two months. A recent complete physical demonstrated decreased DTRs symmetrically, without other abnormal findings. Exam shows shallow, tachypneic respiratory effort.

Case #2

What baseline information is required? PaCO2=40 mm Hg, HCO3=7, pH=6.88 Are the data internally consistent?

Case #2: [H+]~140, which equates to a pH~6.85, so data are internally consistent What is the primary disturbance? ___________ Acidosis Which variable is deranged in a direction which is consistent with acidosis? PaCO2 WNL, ergo, Metabolic Acidosis

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Is compensation appropriate? Metabolic Acidosis PaCO2should fall by 1 to 1.5 mm Hg x the fall in plasma [HCO3]

HCO3 decreased by 17, so we expect PaCO2 to be decreased by 17-26 PaCO2 WNL; since PaCO2 inappropriately high, there is a combinedmetabolic acidosis and respiratory acidosis

Case #3

33 y/o with DKA presents with the following: Na = 128, Cl = 90, HCO3 = 4, Glucose = 800 7.0/14/90/4/95%

Case # 3 What baseline information is required? PaCO2=14 mm Hg, HCO3=4, pH= 7.0 Are the data internally consistent?

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Case # 4 Triple disorder AG acidosis Respiratory acidosis Non AG acidosis

History would suggest AG acidosis is secondary to hypotension with lactic acid build up and the patient is not able to compensate with his COPD therefore there is no respiratory compensation and the non AG acidosis is secondary to diarrhea with associated HCO3 loss.

Case # 4

40 y/o with pneumonia and low BP on dopamine. She has been having N/V over the last three days Na = 130, Cl = 90, HCO3 = 10 ABG = 7.26/15/65/10/90% PH = acidemia AG = 130 (90 + 10) = 30 PC02 = 1.5(10) + 8 = 23 Delta HC03 = 10 + (30 12) = 28

Case #4 Answer AG acidosis Respiratory alkalosis Metabolic alkalosis Patient has sepsis causing AG acidosis and respiratory alkalosis. Previous N/V caused baseline metabolic alkalosis

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Case #5

65 y/o with respiratory failure and COPD ABG on vent. 7.60/40/60/30/90%, HCO3 = 30 Baseline ABG 7.35/60/55/30/88%, HCO3 = 30 Questions: What is wrong with this situation ? What will happen if it is not changed ? How do we fix it ?

Case #5 Vent. ABG = 7.25/35/80/10/95%, HCO3 =10 Questions: What is the acid/base status of the patient ? What equation would you use to determine the changes that need to be made to the ventilator ? What should we do with the ventilator ?

ABG analysis Pitfalls Trying to interpret the acid base status without using the prior formulas Using the HCO3 on the ABG which is calculated (must use the HCO3 from lytes) Not drawing the lytes and ABG at the same time Failing to make sure the ABG correlates with patents clinical situation

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Case # 6

An ill-appearing alcoholic male presents with nausea and vomiting. ABG - 7.4 / 41 / 85 / 22 Na- 137 / K- 3.8 / Cl- 90 / HCO3- 22

Case # 6

Anion Gap = 137 - (90 + 22) = 25 anion gap metabolic acidosis Winters Formula = 1.5(22) + 8 s 2 = 39 s 2 compensated Delta Gap = 25 - 10 = 15 15 + 22 = 37 metabolic alkalosis

Case # 7

22 year old female presents for attempted overdose. She has taken an unknown amount of Midol containing aspirin, cinnamedrine, and caffeine. On exam she is experiencing respiratory distress.

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Case # 7

ABG - 7.47 / 19 / 123 / 14 Na- 145 / K- 3.6 / Cl- 109 / HCO3- 17 ASA level - 38.2 mg/dL

Case # 7 Anion Gap = 145 - (109 + 17) = 19 anion gap metabolic acidosis Winters Formula = 1.5 (17) + 8 s 2 = 34 s 2 uncompensated Delta Gap = 19 - 10 = 9 9 + 17 = 26 no metabolic alkalosis

Case #8

47 year old male experienced crush injury at construction site. ABG - 7.3 / 32 / 96 / 15 Na- 135 / K-5 / Cl- 98 / HCO3- 15 / BUN- 38 / Cr1.7 CK- 42, 346

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Case #8

Anion Gap = 135 - (98 + 15) = 22 anion gap metabolic acidosis Winters Formula = 1.5 (15) + 8 s 2= 30 s 2 compensated Delta Gap = 22 - 10 = 12 12 + 15 = 27 mild metabolic alkalosis

Strong IonsH+ + K+ + Na+ = Cl- + HCO3- + OHYou need electroneutrality, or you would glow. If your blood was saline, Na+ would have to equal Cl-. If you added potassium bicarbonate And then added a bunch of other ions Which ones of these matter, and which are clutter?

Strong IonsMg++ Ca++ K+ Na+ Cl- Others (lactate, etc)

These are the Strong Ions, so-called because they do not readily combine with other ions or lose their charge. Conversely, H+ and HCO3- readily combine, and are called weak ions.

The difference between the strong cations and strong anions is called the Strong Ion Difference (SID), and indicates the net ionic charge of the weak anions; so it indicates the relative strength of H+ and HCO3-.

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Strong Ion DifferenceRemember, SID = strong cations strong anions. It indirectly measures weak ions (HCO3 and A-).

SID = HCO3- + A[Just for the record, HCO3 + A- was called Buffer Base as far back as the 1950s SID was invented by Stewart in 1980.]

You can get HCO3 by Henderson-Hasselbach if you know pCO2 and pH (this is the calculated ABG value). You can get A- if you know ATOT and pH.

Base Excess

Definition: The amount of a strong acid (like HCl) needed to bring blood to 7.40. Assumes 100% oxygenation, 37oC, and pCO2 of 40. Normal = 0

Used to calculate the metabolic component of an acid-base disturbance.

Base Excess calculationsCalculated the same way, in practice, as SID: Buffer Base = HCO3- + AHCO3 calculated by pH & pCO2 (blood gas machine) A- calculated using pH & hemoglobin (whole blood) OR A- calculated using albumin & phos (plasma) BE = Buffer Base expected buffer base (expected if pH = 7.4 and pCO2 = 40)

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Membranes & Ions you guys should feel right at home!

There are flavors of Base Excess: Base ExcessErythrocyte; Base ExcessPlasma; Base ExcessECF(entire extracellular fluid); Base ExcessWhole Blood how do we decide what to use? The Gibbs-Donnan equilibrium describes the behavior whenever a membrane separates impermeable ATOT buffer (Hgb) while allowing passage of other ions (Cl-, HCO3-).

Standard Base Excessaka Base Excess of ECF. ECF includes plasma, red cells, and the surrounding interstitial fluid. Its where the action takes place in the body regarding acidbase movement. Blood-gas machines calculate SBE as: SBE = 0.9287 * (HCO3- - 24.4 + (14.83 * (pH 7.4) And guess what it turns out that ATOT, while fascinating, doesnt really matter clinically. A nice advantage for SBE.

And SBE makes a pretty nomogram.Compare & Contrast:

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And the math is easier.How do you figure out if compensation is normal? In metabolic acidosis, If pCO2 = SBE, then its normal. In metabolic alkalosis, If pCO2 = SBE * 0.6, then its normal.

And the math is easier.In acute respiratory disorders, if SBE = 0 (+/- 5), then its normal. In chronic respiratory disorders, if pCO2 ( 0.4) = SBE, then its normal.

ABG analysis Delta gap Delta HCO3 = HCO3 (electrolytes) + change in AG Delta gap < 24 = non AG acidosis Delta gap > 24 = metabolic alkalosis

Note: The key to ABG interpretation is following the above steps in order.

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Simple Acid-Base Disorders:

The compensatory variable always changes in the SAME DIRECTION as the primarily deranged variable Compensation is always more pronounced in CHRONIC RESPIRATORY disorders than in acute respiratory disorders

8 Sequential Rules:

Rule #4: must know if compensation is appropriate compensation never overshoots Must have known rules of thumb to interpret appropriateness of compensation

Rules of Compensation: Metabolic Acidosis PaCO2 should fall by 1 to 1.5 mm Hg x the fall in plasma [HCO3]

Metabolic Alkalosis PaCO2 should rise by .25 to 1 mm Hg x the rise in plasma [HCO3]

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Rules of Compensation: Acute Respiratory Acidosis Plasma [HCO3] should rise by ~1mmole/l for each 10 mm Hg increment in PaCO2

Chronic Respiratory Acidosis Plasma [HCO3] should rise by ~4mmoles/l for each 10 mm Hg increment in PaCO2

Rules of Compensation: Acute Respiratory Alkalosis Plasma [HCO3] should fall by ~1-3 mmole/l for each 10 mm Hg decrement in PaCO2, usually not to less than 18 mmoles/l

Chronic Respiratory Alkalosis Plasma [HCO3] should fall by ~2-5 mmole/l for each 10 mm Hg decrement in PaCO2, usually not to less than 14 mmoles/l

Case #1:

A 4 year old with chronic renal failure presents to the pedes ER with history of increasing azotemia, weakness, and lethargy. Exam reveals the patient to be modestly hypertensive, and tachypneic. Labs reveal BUN=100, and Creatinine=8. How can we tell if an acid-base disorder is present?

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Case #1:

Steps 1&2: must know pH, PaCO2, HCO3 pH=7.37, PaCO2=22, and HCO3=12 Step 3: are the available data consistent?

?H A! 24 v

PaCO

2

HCO 3

Case #1:

[H+]=44, equates to pH~7.36; data are thus consistent What is the primary disorder? _________Acidosis Which variable (PaCO2, HCO3) is deranged in a direction consistent with acidosis? Primary disorder is Metabolic Acidosis

Is compensation appropriate? HCO3 is decreased by 12 mmoles/l PaCO2 should decrease by 1 to 1.5 times the fall in HCO3; expect PaCO2 to decrease by 12-18 mm Hg or be between 22-28 mm Hg Since PaCO2 is 22 mm Hg, compensation is appropriate, and the data are consistent with a simple metabolic acidosis with respiratory compensation

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Oxygenation


8 Sequential Rules: Rule #5: If the data are consistent with a simple disorder, it does not guarantee that a simple disorder exists; need to examine the patients history

Rule #6: When compensatory responses do not lie within the accepted range, by definition a combined disorder exists.

Case #2:

A 15 year old female is brought to the pedes ER in an obtunded state. Per her family, patient history is notable for progressive weakness/malingering over two months. A recent complete physical demonstrated decreased DTRs symmetrically, without other abnormal findings. Exam shows shallow, tachypneic respiratory effort.

Case #2: Steps 1, 2, and 3 What baseline information is required? PaCO2=40 mm Hg, HCO3=7, pH=6.88 Are the data internally consistent?

?H A! 24 v PaCO HCO

2

3

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Oxygenation


Case #2: +

[H ]~140, which equates to a pH~6.85, so data are internally consistent What is the primary disturbance? ___________ Acidosis Which variable is deranged in a direction which is consistent with acidosis? PaCO2 WNL, ergo, Metabolic Acidosis

Is compensation appropriate? Metabolic Acidosis PaCO2 should fall by 1 to 1.5 mm Hg x the fall in plasma [HCO3]

HCO3 decreased by 17, so we expect PaCO2 to be decreased by 17-26 PaCO2 WNL; since PaCO2 inappropriately high, there is a combinedmetabolic acidosis and respiratory acidosis

Case #3:

A 16 year old male with sickle cell anemia, hemochromatosis, & subsequent cirrhosis, presents with a several day history of emesis. At presentation to the pedes ER, he is hypotensive, orthostatic, and confused. What acid-base disorders might be anticipated based on the above information?

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Oxygenation


Case #3:

16 yo male with sickle cell anemia, hemochromatosis, & subsequent cirrhosis, and several days of emesis. In the pedes ER, he is hypotensive, orthostatic, and confused. Emesis-loss of H+ (HCl)-metabolic alkalosis Orthostatic hypotension-?lactic acidosis SCD-decreased O2 delivery-?lactic acidosis Cirrhosis-decreased lactate metabolism

Case #3:

What baseline information is available? pH=7.55, PaCO2=66 lytes: Na+=166, K+=3.0, Cl-=90, HCO3=56 Are the data internally consistent?

?H A

24

PaCO 2 HCO3

Case #3:

[H+]~28, equates to pH~7.55; consistent What is the primary abnormality? _________ Alkalosis PaCO2oed, HCO3oed, therefore. Metabolic Alkalosis presumed due to emesis Is compensation appropriate?

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Oxygenation


Case #3:

Metabolic Alkalosis PaCO2 should rise by .25 to 1 mm Hg x the rise in plasma [HCO3]

HCO3oed by 32; PaCO2 should o by 8-32 PaCO2 oed by 26, so compensation appears appropriate What about multiple risk factors for lactic acidosis?

Case #3:

Could there be a concealed lactic acidosis? What is the anion gap? Na+- (Cl- + HCO3), normally 12-14 Anion gap here is 166 - (90 + 56) = 20 oed anion gap implies metabolic acidosis Combinedmetabolic alkalosis&metabolic acidosis therefore present

8 Sequential Rules:

Rule #7: Always calculate the anion gap Often it is the only sign of an occult metabolic acidosis acidotic patients partially treated with HCO3 acidotic patients with emesis

May be the only sign of metabolic acidosis concealed by concomitant acid-base disorders

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Oxygenation


Causes of Anion Gap Acidosis: Endogenous acidosis Uremia (uncleared organic acids) Ketoacidosis, Lactic acidosis (increased organic acid production), Rhabdomyolosis

Exogenous acidosis ingestions: salicylate, iron; paraldehyde use

Other Ingestions: Methanol toxicity, Ethylene Glycol toxicity

Anion Gap:

Based on the concept of electroneutrality; the assumption that the sum of all available cations= the sum of all available anions. Restated as: Na+ + Unmeasured Cations (UC) = Cl- + HCO3 + Unmeasure Anions (UA); conventionally restated:

Na+-(Cl-+HCO3)=UA-UC=Anion Gap=12 to 14

Anion Gap: + -

Na -(Cl +HCO3)=UA-UC Serum albumin contributes ~1/2 of the total anion equivalency of the UA pool. Assuming normal electrolytes, a 1gm/dl decline in serum albumin decreases the anion gap factitiously by 3 mEq/L. Therefore an anion gap of 12 mEq/L is corrected to 17-18 mEq/L when the serum albumin is half of normal; this is an important correction factor in settings of chronic illness or malnourished patients

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Occult metabolic acidosis post-Rx:Na + ClHCO 3 ketones AG pH PaCO 2 Normal 140 105 25 0 10 7.40 40 Ketoacidosis 140 105 10 15 25 7.30 31 Post-RX 148 98 25 15 25 7.40 40

Case #4: A 3 year old is brought to the pedes ER at ~3am, stuporous and tachypneic. History is remarkable for his parents having cleaned out their medicine cabinet earlier that day. An ABG and electrolytes have been accidentally drawn by the nurse.

Case #4:

Available data: pH=7.53, PaCO2=12; Na+=140, K+=3.0, Cl-=106, HCO3=10 Are the data internally consistent?

?H A! 24 v PaCO HCO

2 3

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Oxygenation


Case #4:

[H+]~29, so pH~7.51; data consistent What is the primary disturbance? __________ Alkalosis Which variable (PaCO2, HCO3) is deranged in a direction consistent with alkalosis? qed PaCO2, qed HCO3; so Respiratory Alkalosis

Case #4:

Is compensation appropriate? Acute respiratory alkalosis Plasma [HCO3] should fall by ~1-3 mmole/l for each 10 mm Hg decrement in PaCO2, usually not to less than 18 mmoles/l

PaCO2qed by ~30 mm Hg; HCO3 should fall by 3-9 mmole/l; HCO3 q is too great, so superimposed metabolic acidosis

Case #4:

What is the anion gap? 140 - (106 + 10) = 24; elevated anion gap consistent with metabolic acidosis What is the differential diagnosis? Combined (true) respiratory alkalosis and metabolic acidosis seen in sepsis, or salicylate intoxication

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Oxygenation


Case #5:

A 5 year old with Bartters Syndrome is brought to clinic, where she collapses. She has recently been febrile, but history is otherwise unremarkable. An ABG and serum electrolytes are obtained: pH=6.9, PaCO2=81; Na+=142, K+=2.8, Cl-=87, HCO3=16

Case #5:

Are the data consistent?

[H+]=122, pH~6.9; data are consistent

?H A! 24 v PaCO HCO

2 3

Case #5:

What is the primary disturbance? _________ Acidosis Which variable (PaCO2, HCO3) is deranged in a direction consistent with acidosis? Both; pick most abnormal value- Respiratory Acidosis Is compensation appropriate?

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Oxygenation


Case #5:

Acute Respiratory Acidosis Plasma [HCO3] should rise by ~1mmole/l for each 10 mm Hg increment in PaCO2

Since HCO3 is inappropriately depressed, compensation is not appropriate, and there is a concomitant metabolic acidosis as well What is the anion gap? AG=39, confirms metabolic acidosis

Case #5:

Combined Respiratory Acidosis and Metabolic Acidosis; are there other disorders present? What about the dx of Bartters Syndrome? Bartters Syndrome characterized by hypokalemic metabolic alkalosis Does this patient have a concealed metabolic alkalosis?

Case #5:

Anion gap is 39, or 25-27 greater than normal Typically, increases in anion gap correlate with decreases in HCO3 Assuming a 1:1 relationship, as anion gap increases by 25, HCO3 should fall by 25 Starting HCO3 must have been 16 + 25 = 41

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Oxygenation


Case #5:

Therefore, starting HCO3 was ~41 mmol/l, consistent with expected chronic metabolic alkalosis. This metabolic alkalosis was concealed by the supervening profound metabolic and respiratory acidoses associated with her arrest event. Final diagnosis: Metabolic alkalosis, metabolic acidosis, &respiratory acidosis

8 Sequential Rules; Rule #8 Rule #8: Mixed Acid-Base Disorders Coexistant metabolic acidosis and metabolic alkalosis may occur. Always check the change in the anion gap vs. decrement in bicarbonate to rule out a concealed metabolic disorder.

Case #6:

A 3 year old toddler is brought to the ER at 3 am after being found unarousable on his bedroom floor, with urinary incontinence. EMS monitoring at the scene revealed sinus bradycardia. One amp of D50W and 5 mg of naloxone were given IV without response. Vital signs are stable; respiratory effort is regular, but tachypneic. He is acyanotic.

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Oxygenation


Case #6:

Initial lab studies (lytes, ABG & urine tox screen) are sent. Initial dextrostick is >800. Initial available data are: Na+=154, K=5.6, Cl=106, HCO3=5, BUN=6 creatinine=1.7, glucose=804, PO4=12.3, Ca++=9.8, NH4=160, serum osms=517 pH=6.80, PaCO2=33, PaO2=298

Case #6:

What is the primary disturbance? ________ Acidosis Metabolic Acidosis Is compensation appropriate? No; PaCO2 level is inappropriately high Are other disorders present? Respiratory acidosis (due to evolving coma)

Case #6:

What is our differential thus far? Anion gap vs. non-anion gap metabolic acidosis DKA, lactic acidosis, renal failure, ingestion

The urine tox screen comes back negative What does urine tox screen actually screen for?

The patients IV falls out. He then has a seizure, is incontinent of urine, and fills the specimen bag you placed on ER arrival.

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Case #6:

What is the calculated serum osmolality, and does an osmolal gap exist? 2(Na) + BUN/2.8 + Glucose/18 Calculated=355, Measured=517

What is the most likely diagnosis? How can this be confirmed definitively? Review of urinalysis Serum ethylene glycol level

How Many Primary Abnormalities Can Exist in Three primary abnormalities is the max because a One Patient? person cannot simultaneously hyper andhypoventilate One patient can have both a metabolic acidosis and a metabolic alkalosis usually one chronic and one acute

POINT!!!!! Rapid respiratory rate is assumed to be compensatory for metabolic acidosis until proven otherwise

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Oxygenation


POINT!!!! Wide Anion Gap Used to confirm type of metabolic acidosis with ABG Used to diagnose metabolic acidosis without ABG Affected by: albumin (for each 1 gm decrease in albumin , add three points to gap) hyperchloremia (usually from fluid resuscitation) High Cl- causes decrease in available HC03 High Cl- binds to H+ HCl Cannot compensate because is not a compound that can be blown off Metabolic acidosis with normal gap: non-gap acidosis most commonly occurs in hyperchloremia

So what about lactate?

Lactate

Is serum Lactate a good marker of adequacy of perfusion?

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Oxygenation


Lactate Levels

Lactic acid is a product of carbohydrate metabolism. Normal to produce 15 to 20 mmol/kg per day Normal plasma level is 0.5 to 1.5 meq/L Hyperlactatemia is considered to be present if the level exceeds 4 to 5 meq/L

Lactic acid is rapidly buffered by extracellular bicarbonate resulting in lactate. Liver and kidneys convert lactate back to pyruvate which is then converted to CO2 & H2O or glucose

Lactate

Lactate production results from cellular metabolism of pyruvate into lactate under anaerobic condition blood lactate level in type A lactic acidosis is related to the total oxygen debt and the magnitude of tissue hypoperfusion

Lactate

type A lactic acidosis, resulting from an imbalance between tissue oxygen supply and demand Elevated blood lactate levels associated with metabolic acidosis are common among critically ill patients with systemic hypoperfusion, tissue hypoxia and metabolic dysfunction

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Oxygenation


Targeting Lactate use as index of hypoperfusion in sepsis complicated by several factors elevation may reflect reduced elimination, not increased production epinephrine surge stimulates Na, K-ATPase and promotes glycolysis pyruvate dehydrogenase enzyme dysfunction in sepsis some organs produce more lactate than others elevation may depend upon the particular organ compromised from sepsis

Targeting: Blood Lactate no study has targeted correction of lactate per se high lactate levels in critically ill patients associated with increased mortality (Bakker et al. Chest 1991) utility of a single high initial lactate debated poor sensitivity and specificity

lactate clearance better predictor of mortalityBakker et al. (Am J Surg 1996) lac-time: time in which blood lactate > 2 mmol/l survivors had decreased lac-time lac-time also directed correlated with number of organ failures

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Oxygenation


Targeting: Blood Lactate

Nguyen et al. Crit Care Med 2004

serial lactate levels may improve the prognostic value and help guide therapy

Physiologic Effects of Acidosis contractility Reduced cardiac Pulmonary vasoconstriction Reduced systemic vascular tone Impaired response to catecholamines Compensatory hyperventilation Hypotension +Hyperventilation= THINK ACIDOSIS!!!

DKA defined

A life threatening complication of diabetes (usually Type I) which requires a prompt, organized, and rational approach to treatment to minimize morbidity and mortality

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Oxygenation


Lab criteria for DKA

All three criteria of the following criteria are required to make the diagnosis of DKA: hyperglycemia (BG > 250 mg/dl) low bicarbonate (< 15 meq/l) low pH (< 7.3) with ketonemia

Ketones and acidosis

Acidosis can be due to keto-acids (DKA) but can be due to many other causes (both gap and non-gap)

Patients who have not eaten in > 12 hours may have low level starvation ketones

Anion Gap and Ketones

DKA - waste products of non-glucose dependent pathway produce ketones (betahydroxybutyrate and acetoacetate) that are acids (H+/anion) build up in the blood stream (increase in anion gap)

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Oxygenation


Lactic AcidosisWhy do we need oxygen? For oxidative phosphorylation What is oxidative phosphorylation? ADP + Pi = ATP (requires energy) The formation of ATP What does the oxygen do?

Glycolysis:GlucosePyruvateAcetyl CoA Krebs:Acetyl CoANADH & FADH Electron transport chain (ETC) NADH & FADHATP

Lactic Acidosis

Lactic Acidosis The bulk of ATP is generated in the electron transport chain (ETC) in the mitochondrion The energy for creating the high-energy phosphate bond is generated at several points in the ETC. So are hydrogen ions

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Oxygenation


Metabolic AcidosisHigh (primary fall in serum bicarbonate)

Oxygen allows for ATP formation in an electrically-neutral biologically safe manner electrically-

Metabolic Acidosis(primary fall in serum bicarbonate)

Lactic Acidosis Type A: failure of oxidative phosphorylation ( ) Type B: lactate production lactate metabolismPyruvate Lactate

overwhelms

Lactic Acidosis Type A ETC: Failure of (more severe)

Decreased Oxygen deliveryShock of any type Severe hypoxemia Severe Anemia Inhibitors (CO, CN)

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Oxygenation


Lactic Acidosis Type B (lessoverwhelms lactate metabolism Lactate production severe)(not anaerobic) Malignancies (after chemotherapy) Hepatic failure Drugs (biguanides, AZT, INH)

Acid/Base

Metabolic alkalosis Removal of gastric secretions Factitious Diarrhea (laxatives) Mineral corticoid excess Diuretics Posthypercapnic alkalosis Milk alkali syndrome

Metabolic Alkalosis Volume Contraction: Chloride responsive NG suction Vomitting Diuretics

Post Hypercapnia Hypokalemia Hypomagnesemia Carbenicillin, Penicillin

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Oxygenation


Metabolic Alkalosis Chloride Unresponsive Adrenal Disorders Glucocorticoid Excess Mineralcorticoid Excess

Exogenous Steroids Alkali Ingestion Licorice Bartters Syndrome

Metabolic Alkalosis Signscramps Symptoms Muscle and Weakness Hypoxia Arrhythmias

Lactate Lactate Levels Levels The other acid: Lactic acid is a product of carbohydrate metabolism. It is normal to produce 15 to 20 mmol/kg of lactic acid per day. The normal plasma level is 0.5 to 1.5 meq/L Hyperlactatemia is considered to be present if the level exceeds 4 to 5 meq/L. Lactic acidosis is considered to be present if the elevated lactate level is in conjunction with a gap >20 in the absence of elevated glucose /ketosis.

Lactic acid is rapidly buffered by extracellular bicarbonate resulting in lactate. The liver and kidneys convert lactate back to pyruvate which is then converted to CO2& H2O or glucose.

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Lactate Levels

Is serum Lactate a good marker of adequacy of perfusion? Increased lactate production results from cellular metabolism of pyruvate into lactate under anaerobic conditions. When lactate elevated there are two questions to ask? What is the history and the evidence for acidosis? If tissues hypoxic, Serum bicarbonate cannot neutralize all the lactic acid to lactate, acidosis occurs (Type A lactic acidosis)

Is there a metabolic pathway or clearance problem? Typically not acidotic ( Type B lactic acidosis )

Lactate Levels Is serum Lactate a good marker of adequacy of perfusion? Type A lactic acidosis primarily results from an imbalance between tissue oxygen demand, delivery and use. The blood lactate level in type A lactic acidosis is related to the total oxygen debt and the magnitude of tissue hypoperfusion.

Elevated blood lactate levels associated with metabolic acidosis are common among critically ill patients with systemic hypoperfusion, tissue hypoxia and metabolic dysfunction.

Blood lactate levels also increase with clearance failure , i.e., kidney or liver dysfunction

Lactate LevelsTargeting: Blood Lactate No study has targeted correction of lactate per se. High lactate levels in critically ill patients have been associated with increased mortality1 . Utility of a single high initial lactate have been debated poor sensitivity and specificity Lactate clearance is a better predictor of mortality2,3 . Lac-time: time it takes to clear 10% of lactate Time to clear < 24 hours , improves survival in Severe sepsis Lac-time also directly correlated with number of organ failures

One lactate (lactic acid ) level is not as predictive or evaluative as a series over 24 hours ( i.e., Q6H)1. 2. 3. Bakker, J., Coffernils, M., Leon, M., Vincent, J.L. (1991). Blood lactate levels are superior to oxygen-derived variables in predicting outcomes in human patient shock. Chest, 99, 956-962. Bakker, J., Gris, P., Coffernils, M., Kahn R.J., Vincent, J.L. (1996). Serial blood lactate levels can predict the development of multiple organ failure following septic shock. Am J Surg, 171(2), 221-226. Nguyen, H.B., Rivers, E.P., Knoblich, B.P., et al. (2004). Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med, 32(8), 1637-1642.

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Oxygenation


Lactic Acid Table

Targeting Blood Lactate Conclusion3: Serial lactate levels may improve the prognostic value and help guide therapy

3.

Nguyen, H.B., Rivers, E.P., Knoblich, B.P., et al. (2004). Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med, 32(8), 1637-1642.

Lactate LevelsCO2 21, pH 7.31, HCO311, Na 141, Cl 96 Problem? Acute metabolic acidosis (situational respiratory acidosis) Anion gap: 141 (96 +11) = 34 Lactic Acid Level: 8.9 HR 148 RR 27 Compensatory in order to oxygen delivery and carbonic acid

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Oxygenation


SummaryPhysiologic effects of acidosis Reduced cardiac contractility Pulmonary vasoconstriction Reduced systemic vascular tone Impaired response to catecholamines Compensatory hyperventilation Hypotension + Hyperventilation = THINK ACIDOSIS!!!

Understanding Tissue OxygenComponents of Oxygen Delivery 1. Cardiac Output = Heart rate x stroke volume 2. Total hemoglobin (02 carrying capacity) 3. Saturation of hemoglobin First line compensatory mechanism ( patient) Increase the heart rate and stroke volume to increase delivery when cells are hypermetabolic and/or when oxygen is not functionally dissociating from its transporter, hemoglobin.

Lactate Lactate Levels Levels The other acid: Lactic acid is a product of carbohydrate metabolism. It is normal to produce 15 to 20 mmol/kg of lactic acid per day. The normal plasma level is 0.5 to 1.5 meq/L Hyperlactatemia is considered to be present if the level exceeds 4 to 5 meq/L. Lactic acidosis is considered to be present if the elevated lactate level is in conjunction with a gap >20 in the absence of elevated glucose /ketosis.

Lactic acid is rapidly buffered by extracellular bicarbonate resulting in lactate. The liver and kidneys convert lactate back to pyruvate which is then converted to CO2& H2O or glucose.

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Oxygenation


Lactate Levels

Is serum Lactate a good marker of adequacy of perfusion? Increased lactate production results from cellular metabolism of pyruvate into lactate under anaerobic conditions. When lactate elevated there are two questions to ask? What is the history and the evidence for acidosis? If tissues hypoxic, Serum bicarbonate cannot neutralize all the lactic acid to lactate, acidosis occurs (Type A lactic acidosis)

Is there a metabolic pathway or clearance problem? Typically not acidotic ( Type B lactic acidosis )

Lactate Levels Is serum Lactate a good marker of adequacy of perfusion? Type A lactic acidosis primarily results from an imbalance between tissue oxygen demand, delivery and use. The blood lactate level in type A lactic acidosis is related to the total oxygen debt and the magnitude of tissue hypoperfusion.

Elevated blood lactate levels associated with metabolic acidosis are common among critically ill patients with systemic hypoperfusion, tissue hypoxia and metabolic dysfunction.

Blood lactate levels also increase with clearance failure , i.e., kidney or liver dysfunction

Lactate LevelsTargeting: Blood Lactate No study has targeted correction of lactate per se. High lactate levels in critically ill patients have been associated with increased mortality1 . Utility of a single high initial lactate have been debated poor sensitivity and specificity Lactate clearance is a better predictor of mortality2,3 . Lac-time: time it takes to clear 10% of lactate Time to clear < 24 hours , improves survival in Severe sepsis Lac-time also directly correlated with number of organ failures

One lactate (lactic acid ) level is not as predictive or evaluative as a series over 24 hours ( i.e., Q6H)1. 2. 3. Bakker, J., Coffernils, M., Leon, M., Vincent, J.L. (1991). Blood lactate levels are superior to oxygen-derived variables in predicting outcomes in human patient shock. Chest, 99, 956-962. Bakker, J., Gris, P., Coffernils, M., Kahn R.J., Vincent, J.L. (1996). Serial blood lactate levels can predict the development of multiple organ failure following septic shock. Am J Surg, 171(2), 221-226. Nguyen, H.B., Rivers, E.P., Knoblich, B.P., et al. (2004). Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med, 32(8), 1637-1642.

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Lactate LevelsTargeting Blood LactateConclusion : Serial lactate levels may improve the prognostic value and help guide therapy3

3.

Nguyen, H.B., Rivers, E.P., Knoblich, B.P., et al. (2004). Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med, 32(8), 1637-1642.

Lactate LevelsCO2 21, pH 7.31, HCO311, Na 141, Cl 96 Problem? Acute metabolic acidosis (situational respiratory acidosis) Anion gap: 141 (96 +11) = 34 Lactic Acid Level: 8.9 HR 148 RR 27 Compensatory to oxygen delivery and carbonic acid

SummaryPhysiologic effects of acidosis Reduced cardiac contractility Pulmonary vasoconstriction Reduced systemic vascular tone Impaired response to catecholamines Compensatory hyperventilation Hypotension + Hyperventilation = THINK ACIDOSIS!!!

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Understanding Scv02

Understanding Tissue OxygenTissue Oxygenation The single MOST important issue is tissue oxygenation. All physiologic components are designed to maintain balanced tissue oxygen consumption (demand). What are the components of Oxygen Consumption? Oxygen delivery Metabolic demand at the cellular level Blood flow through the capillary Ability to dissociate oxygen from hemoglobin

Tissue Oxygenation There are two mechanisms designed to meet oxygen consumption (demand) Increase oxygen delivery Increase the release (dissociation) of oxygen from hemoglobin

Understanding Tissue Oxygen

In the best of critical situations, both delivery and dissociation increase to maintain cells failure of one mechanism will be supported by compensation by the other

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Understanding Tissue Oxygen In normal situations, short, intermittent increases in oxygen consumption are supported with rapid temporary compensation: increased oxygen delivery and a more rapid dissociation of oxygen

Oxyhemoglobin Dissociation

OXYGEN Delivery

OXYGEN Demand & Consumption

Understanding Tissue Oxygen Components of Oxygen Delivery 1. Cardiac Output = Heart rate x stroke volume 2. Total hemoglobin (02 carrying capacity) 3. Saturation of hemoglobin First line compensatory mechanism ( patient) Increase the heart rate and stroke volume to increase delivery when cells are hypermetabolic and/or when oxygen is not functionally dissociating from its transporter, hemoglobin.

Understanding Tissue What is the purpose of saturating hemoglobin? Oxygen Hemoglobin is the transporter of oxygen Each heme molecule binds 1.34 mLs of oxygen

When oxygen is bound it is not usable Measure of bound oxygen in the arterial blood is the Sa02 (indirectly reflected by pulse oximetry Sp02)

Only oxygen dissolved in blood can be used Measure of dissolved oxygen in the arterial blood is the Pa02

The rate of oxygen use at the cell determines the Pa02 which in turn affects the dissociation

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Understanding Tissue OxygenArterial measures reflect the amount of oxygen available but do not reflect the cell use

Understanding Tissue Oxygen The amount of oxygen required by the cells changes every second When demand/consumption increases, hemoglobin releases oxygen more rapidly Shift to the right: release

When demand/consumption decreases, hemoglobin decreases release or latches on to oxygen Shift to the left: latched on

Second compensatory mechanism: hemoglobin more aggressively releases oxygen to dissolve in the blood (partial pressure) to be used by the cells

Understanding Tissue Oxygen dissociation as a compensatory response Oxygen Shifts in the bound oxygen mean that there is a change in the way oxygen is Taken up by the hemoglobin molecule at the alveolar level (Sa02) Depends on the partial pressure of alveolar gas (PA02)

Released related to the partial pressure of capillary oxygen (Pa02, Pcap02) Capillary oxygen depends on the tissue oxygen (Pti02) Tissue oxygen goes down when cells are hypermetabolic and/or the delivery is inadequate

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Understanding Tissue What affects oxygen Oxygen dissociation? Hemoglobin has a steady and predictable affinity for oxygen in a normal environment In acidosis ( signal that demand/consumption ), hemoglobin releases oxygen more rapidly In alkalosis (signal that demand/consumption ), hemoglobin decreases the release of oxygen Capillary integrity Amount and integrity of hemoglobin Enzymes required to release oxygen from hemoglobin (shifting) Shifting Determined by the partial pressure of dissolved oxygen in the space (gas or fluid) surrounding the hemoglobin

OxygenationPulmonary Arteries = 40 mm Hg, 70% saturated Blood goes through pulmonary capillaries: oxygenates Pulmonary Veins =100 mm Hg, 100% saturated Systemic Arteries = 95 mm Hg, 99% saturated Blood goes through systemic capillaries: releases oxygen, variable de-saturated Central Veins = 40 mm Hg, 70% saturated,

But

Sa02 is pre-cell reservoir: 95-100% Sv02 is post cell left over: 60-80% Scv02 is global (upper extremities) post cell left over: 65-85%

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Oxygenation


Understanding Tissue Oxygen Measuring Oxygen Dissociation True Oxygen dissociation can only be measured in the venous compartment Small veins represent only the tissues distal to them Large veins ( central or pulmonary artery) reflect a large surface area Central vein : SVC : Scv02: saturation of central venous oxygen (less the IVC and the coronary sinus) IVC, SVC & Coronary Sinus: Sv02: mixed in the RA and the RV then measured in the pulmonary artery (carrying total venous outflow including coronary sinus)

Understanding Tissue Measuring saturation Oxygen in the central or mixed venouscirculation Dissociation of oxygen from hemoglobin is a life saving compensatory mechanism when tissue demand increases beyond the oxygen delivery compensatory capabilities Sv02 ( mixed venous requiring a pulmonary artery catheter): normal is 60-80 % saturation of hemoglobin (reserve in case of emergency: never meant for standard use). When venous saturation decreases < 60%, this measure indicates that the cells are using a greater amount of the reserve. Cannot continue in this emergency state Therapy: increase delivery, decrease demand

Understanding Tissue Oxygen Measuring saturation in the central venous circulation(cont)1,2,3,4 A triple lumen catheter with an oximetry tip can be inserted into the SVC in order to give an indirect (surrogate) measure of Sv02 Scv02 normal is 65-85 %, may have up to a 15% difference from the Sv02. Less invasive Within 5-15% of Sv02 Provides reliable endpoint tissue measure for resuscitationDueck, M.H., Klimek, M., Appenrodt, S., Weigand, C., Boerner, U. (2005). Trends but Not Individual Values of Central Venous Oxygen Saturation Agree with Mixed Venous Oxygen Saturation during Varying Hemodynamic Conditions. Anesthesiology, 103(2), 249257. Reinhart, K., Kuhn, H., Hartog, C., Bredle, D.L.. (2004). Continuous central venous and pulmonary artery oxygen saturation monitoring in the critically ill. Intensive Care Med, 30(8), 1572-1578. Rivers, E., Nguyen, B., Havstad, S., et al. (2001). Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med, 345, 13681377. Tahvanainen, J., Meretoja, O., Nikki, P. (1982). Can central venous blood replace mixed venous blood samples? Crit Care Med, 10(11), 758761.

1. 2. 3. 4.

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Tissue Oxygnation Measures

mixed venous oxygen saturation (SvO2) balance between systemic oxygen delivery and consumption during treatment of critically ill patients central venous oxygen saturation (ScvO2) reflects degree of oxygen extraction from brain and upper part of body beneficial effects on patient outcome by continuous measurement----------Rivers et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. NEJM 2001; 345:13681377.

Oxygenation Patterns with Normal Function

Alveoli

Sv02 :0.6

0.8

RV RA Cell Scv02 :0.65- 0.85

LA LV

Sa02 :0.95

1.0

Venous Oxygenation Patterns

Dissociation must be measured in the venous compartmen t

Sv02 Scv02

Pv02

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Compensation in attempts to sustain Tissue Oxygen

OXYGEN releaseCOMPENSATION: Shift to the right Release oxygen to save the cells MEASURE: Scv02 Always Compensatory Always an EMERGENCY

PROBLEM Oxygen delivery inadequate for oxygen demand Primary failure

OXYGEN DeliveryOXYGEN Demand & Consumption

Compensation Oxygenation

Sv02 Scv02 Low Pv02

Compensation in attempts to sustain Tissue OxygenPROBLEM Scv02 normal to in the face of suspicion (HR , RR persistent acidosis (LA)) MUST BE considered as failure to release oxygen (in the presence of LA)

OXYGEN DeliveryCOMPENSATION: Cardiac output increases Despite increase, tissue hypoperfusion persists ( LA)

OXYGEN release OXYGEN Demand & Consumption

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Sv02 Normal to High With Persistent Lactic Acidosis

Cells do not need it! OR Cells need it but cannot get it!

Pv02

Mixed Venous Gas ScvO2 is usually more than SvO2 by about 23% but two change in parallel In septic shock ScvO2 often exceeds SvO2 by about 8% correlation between these two parameters may worsen

ScvO2should not be used alone in assessment of cardiocirculatory system

Time Matters in the Treatment of Sepsis

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The Biggest Issue is Oxygen Scv02= 74% Serum C02 = 12 AG = 25 HR 148

Everything OK? What is the problem (if any)





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Compensation in attempts to sustain Tissue OxygenCO2 21, pH 7.31, HCO3 11, Na 141, Cl 96 Problem? Acute metabolic acidosis Anion gap: 141 (96 +11) = 34 Lactic Acid Level: 8.9 Scv02= 74% HR 148 RR 27 Everything OK? What is the problem (if any)


Despite apparent compensation (assuming Cardiac output and RR) the patient continues in acute metabolic and lactic acidosis with a wide anion gap. The Scv02 of 74% indicates that the patient has oxygen in the reserve, and in the face of untoward cellular demand (indicated by the lactic acid and metabolic acidosis), he is unable to use it!

Treatment Consider adequacy of intra vascular volume, red cells, inotropes After assuring arterial volume, consider reduction of vasopressors (if any) and in the face of severe sepsis, consider rhAPC.

Compensation in attempts to sustain Tissue OxygenCO2 31, pH 7.34, HCO3 17, Na 134, Cl 100 Problem? Acute metabolic acidosis Anion gap: 134 (100 +17) = 17 Lactic Acid Level: 5.1 Scv02= 51% HR 126 RR 24 Everything OK? What is the problem (if any)

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Compensation in attempts to sustain Tissue OxygenDelivery of oxygen is not compensating for cellular demand. The patient is maintaining function (barely) secondary compensation: shifting oxygen off of hemoglobin at the capillary level. While he is maintaining himself at this moment the possibility that he may decompensate is very real. Treatment Evaluate cardiac efficiency Increase sedation and analgesia to decrease demand Consider adequacy of intra vascular volume, red cells, inotropes .

Tissue OxygenTherapeutic Maintenance of Oxygenation in Sepsis Increase Da02 : O2 delivery Decrease V02 :O2 consumption Improve O2 appropriate use Improve delivery Volume Inotropes PRBC

Volume Inotropes PRBC

Sedation Analgesia Normothermia

Improve capillary flow Decrease demand Decrease vasopressors Consider rhAPC

Practical Approach1. Check the pH any variation from perfectIf the pH < 7.35, acidemia (and at least 1 acidosis) is present. If the pH > 7.45, alkalemia (and at least 1 alkalosis) is present.

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Practical Approach2. Check the pCO2 Any variation from perfect pH < 7.35 and pCO2< 40 metabolic acidosis pH < 7.35 and pCO2> 40 respiratory acidosis pH > 7.45 and pCO2< 40 respiratory alkalosis pH > 7.45 and pCO2> 40 metabolic acidosis

Practical Approach3. Choose the appropriate compensation formulaMost prominent disorder Metabolic acidosis Metabolic alkalosis Respiratory acidosis Compensation formula pCO2 1.5 [HCO3-] + 8 pCO2 0.9 [HCO3-] + 16 For every 10 in pCO2, pH decreases by: 0.08 (in acute resp. acidoses) 0.03 (in chronic resp. acidoses) For every 10 in pCO2, pH increases by: 0.08 (in acute resp. alkaloses) 0.03 (in chronic resp. alkaloses)

Respiratory alkalosis

Practical Approach4. Determine if the degree compensation is appropriate(If it isnt, a second acid-base disorder is likely present)

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Practical Approach5. Calculate the anion gapAnion gap = [Na+] ( [Cl-] + [HCO3-] )

If the anion gap is elevated, an elevated gap metabolic acidosis is likely present.

Practical Approach6. If an elevated gap acidosis is present, calculate the delta-delta ratio, to determine if a second metabolic disorder is present.DeltaDelta = Measured anion gap Normal anion gap Normal [HCO3-] Measured [HCO3-]

Practical Approach7. If a metabolic acidosis is present, check the urine pH.Urine pH > 6.0 in the setting of an acidosis Suggests RTA

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Practical Approach8. Generate a differential diagnosis

If multiple disorders are present, they may be: All related to the same process All independent of one another

Summary of the Approach to ABGs1. 2. 3. 4. 5. 6. 7. 8. Check the pH Check the pCO2 Select the appropriate compensation formula Determine if compensation is appropriate Check the anion gap If the anion gap is elevated, check the delta-delta If a metabolic acidosis is present, check urine pH Generate a differential diagnosis

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acid and anion

Documents

acid co2

acid hco3

acid presence

acid estimates

metabolic h

acidbase balanceimbalance

shift of carbonic acid

respiratory ph